Kdr genotyping in Aedes aegypti from Brazil on a nation-wide scale from 2017 to 2018

Abstract

insecticide resistance is currently a threat to the control of Aedes agypti, the main vector of arboviruses in urban centers. Mutations in the voltage gated sodium channel (Na V), known as kdr (knockdown resistance), constitute an important selection mechanism for resistance against pyrethroids. in the present study, we investigated the kdr distribution for the Val1016Ile and Phe1534Cys alterations in Ae. aegypti from 123 Brazilian municipalities, based on SNP genotyping assays in over 5,500 mosquitoes. The alleles Na V S (1016Val + + 1534Phe +), Na V R1 (1016Val + + 1534Cys kdr) and Na V R2 (1016Ile kdr + 1534Cys kdr) were consistently observed, whereas kdr alleles have rapidly spread and increased in frequency. Na V S was the less frequent allele, mostly found in northeastern populations. the highest allelic frequencies were observed for Na V R1, especially in the North, which was fixed in one Amazonian population. The double kdr Na V R2 was more prevalent in the central-west and Southeastern populations. We introduce the 'kdr index', which revealed significant spatial patterns highlighting two to three distinct Brazilian regions. The 410L kdr mutation was additionally evaluated in 25 localities, evidencing that it generally occurs in the Na V R2 allele. this nationwide screening of a genetic mechanism for insecticide resistance is an important indication on how pyrethroid resistance in Ae. aegypti is evolving in Brazil. The number of dengue cases in Brazil totaled over 1.9 million records between 2016 and 2018. During the same period, the recent additional chikungunya and Zika arbovirus epidemics were responsible for around 540 and 240 thousand cases, respectively, according to Ministry of Health official bulletins 1. Failure in the control of Aedes aegypti, so far considered the primary vector of the aforementioned arboviruses in Brazil, is considered the main reason for the increase in these records. Despite a series of studies evidencing arbovirus transmission by Brazilian Aedes albopictus populations, this species probably acts as a secondary urban vector, mostly significant in maintaining arbovirus circulation during inter-epidemic seasons and in rural regions 2,3. The measures for controlling the density of Aedes mosquitoes largely rely on insecticides. However, their intense use has been, increasingly, selecting resistant populations at a global scale 4. This is also true in Brazil, where an extensive insecticide resistance monitoring system has tracked the susceptibility status of Ae. aegypti populations since 1999 5,6. Organophosphate application has been intensified since the 1980s, substituted by insect growth regulators and pyrethroids two decades later, against larvae and adults, respectively, given the confirmation of resistance to the larvicide temephos 7. However, pyrethroid resistance was also confirmed a few years later 8 .

Large-scale deployment and establishment ofWolbachiainto theAedes aegyptipopulation in Rio de Janeiro, Brazil

“…The copyright holder for this preprint this version posted April 30, 2021. ; https://doi.org/10.1101/2021.04.29.441982 doi: bioRxiv preprint the voltage-gated sodium channel (Nav), known as kdr (knockdown resistance), in field caught Wolbachia + samples from RJ1 and RJ2 (Figure 5). As we could observe, the allelic profiling of samples from both intervention areas revealed the predominance of resistant variants, NavR1(1016Val + , 1534Cys kdr ) and NavR2 (1016Ile kdr , 1534Cys kdr ), and shortage of the susceptible one, NavS (1016Val + , 1534Phe + ), corroborating the findings of a nation-wide survey (Melo Costa et al 2020). Over the monitoring period, this profile experienced little variation within and between areas, indicating the long-term maintenance of kdr mutations in wMel-infected field samples, and highlighting its adaptive role in pyrethroid-infested environments.…”

High larvicidal efficacy of yeast-encapsulated orange oil against Aedes aegypti strains from Brazil

“…We recently collected a third resistant strain from a region well known for its history of insecticide resistance in Ae. aegypti , Belo Horizonte [ 35 , 38 ]. The resistance ratios for 50%, 90%, and 95% mortality (RR 50–95 ) for all strains were below 5.…”

“…This collection was performed during January 2018 in the northeastern area of Belo Horizonte city (19°49′13″ S, 43°55′06″ W), and eggs were hatched and maintained at Oswaldo Cruz Institute in Fiocruz. Each strain was identified as susceptible or resistant based on susceptibility to the insecticides deltamethrin (PY) and temephos (OP) as determined by dose–response bioassays on their initial generations F1–2 and literature data [ 35 – 38 ]. The information about the susceptibility/resistance profile of Belo Horizonte is only qualitative because we were unable to obtain information about insecticide screening for this strain.…”

“…Fludora ® Fusion, Bayer, Germany) during disease outbreaks (e.g. dengue, chikungunya), and the mosquito population presents a high proportion of Kdr alleles [ 35 , 38 ]. In addition, we used the Rockefeller strain as the reference for Ae.…”

“…TO: Tocantins; AP: Amapá; MG: Minas Gerais. RR 50 : values calculated by dose–response bioassays using Rockefeller as reference strain for Caseara, Oiapoque, and Macapá, while qualitative information for Belo Horizonte is presented based on the literature [ 35 , 38 ]. Resistant: strains were labeled as resistant with diagnostic dose assays carried out on initial generations (F1–2)…”